PURPOSE: To summarise recommendations about 20 non-surgical interventions for recent onset (<12 weeks) non-specific low back pain (LBP) and lumbar radiculopathy (LR) based on two guidelines from the Danish Health Authority.

METHODS: Two multidisciplinary working groups formulated recommendations based on the GRADE approach.

RESULTS: Sixteen recommendations were based on evidence, and four on consensus. Management of LBP and LR should include information about prognosis, warning signs, and advise to remain active. If treatment is needed, the guidelines suggest using patient education, different types of supervised exercise, and manual therapy. The guidelines recommend against acupuncture, routine use of imaging, targeted treatment, extraforaminal glucocorticoid injection, paracetamol, NSAIDs, and opioids.

CONCLUSION: Recommendations are based on low to moderate quality evidence or on consensus, but are well aligned with recommendations from international guidelines. The guideline working groups recommend that research efforts in relation to all aspects of management of LBP and LR be intensified.

The nocebo effect is defined as the incitement or the worsening of symptoms induced by any negative attitude from non-pharmacological therapeutic intervention, sham, or active therapies. When a patient anticipates a negative effect associated with an intervention, medication or change in medication, they may then experience either an increase in this effect or experience it de novo. Although less is known about the nocebo effect compared with the placebo effect, widespread interest in the nocebo effect observed with statin therapy and a literature review highlighting the nocebo effect across at least ten different disease areas strongly suggests this is a common phenomenon. This effect has also recently been shown to play a role when introducing a medication or changing an established medication, for example, when switching patients from a reference biologic to a biosimilar. Given the important role biosimilars play in providing cost-effective alternatives to reference biologics, increasing physician treatment options and patient access to effective biologic treatment, it is important that we understand this phenomenon and aim to reduce this effect when possible. In this paper, we propose three key strategies to help mitigate the nocebo effect in clinical practice when switching patients from reference biologic to biosimilar: positive framing, increasing patient and healthcare professionals' understanding of biosimilars and utilising a managed switching programme.

OBJECTIVE: To present the evidence for nutritional lifestyle changes recommended for gout patients; an explicit focus will be on the evidence for weight loss in overweight gout patients based on a recent systematic review and to describe methodological details for an upcoming weight loss trial.

METHODS: We did a pragmatic but systematic search in MEDLINE for current guidelines that had made an attempt to make nutritional recommendations for gout. The quality of the evidence for the nutritional recommendations was evaluated based on the guidelines' own ratings and converted into a common simple version based on the GRADE system. The recently published systematic review on weight loss for gout, was based on six databases from which longitudinal studies that had quantified the effects following weight loss were included. The internal validity was assessed with the ROBINS-I tool and the quality of the evidence was assessed with the GRADE approach. Based on the results of the systematic review, a trial was designed, adhering to the principles of evidence based research.

RESULTS: We included 17 guidelines. Most guidelines recommend avoiding or limiting alcohol intake (15; i.e. 88%), lose weight if relevant (12; 71%), and reduce fructose intake (11; 65%). The majority of the evidence for the nutritional recommendations was rated Moderate/Low or Very Low quality. Our recent systematic review on weight loss included 10 studies and found that the available evidence indicates beneficial effects of weight loss for overweight and obese gout patients, but the evidence is of low to moderate quality. As a consequence, researchers from the Parker Institute are launching a randomized trial to explore the short-term effects related to a diet-induced weight loss in obese gout patients.

CONCLUSIONS: The nutritional recommendations for gout are generally based on low quality evidence. In terms of weight loss as a management strategy, the available evidence is in favor of weight loss for overweight/obese gout patients. However, since the current evidence consists of only a few studies (mostly observational) of low methodological quality, the Parker Institute are now initiating a rigorous exploratory randomized trial. Similar efforts are needed for other nutritional management strategies for gout.

OBJECTIVE: To test long-term effectiveness of neuromuscular exercise (NEMEX) with instructions in optimized pharmacological treatment (PHARMA) on activities of daily living (ADL) in patients with early knee osteoarthritis.

DESIGN: 12-months follow-up from a randomized controlled trial. Participants with mild-to-moderate medial tibiofemoral knee osteoarthritis were randomly allocated to 8 weeks NEMEX or PHARMA. The primary outcome measure was the ADL-subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS). Secondary outcome measures included the other four KOOS-subscales, the University of California Activity Score (UCLA) and the European Quality of Life-5 Dimensions.

RESULTS: Ninety-three patients (57% women, 58 ± 8 years, body mass index 27 ± 4 kg/m2) were randomized to NEMEX (n = 47) or PHARMA group (n = 46) with data from 85% being available at 12-months follow-up. Good compliance was achieved for 49% of the participants in NEMEX (≥12 sessions) and 7% in PHARMA (half the daily dose of acetaminophen/NSAIDs ≥ 28 days). Within-group improvements in NEMEX were considered to be clinically relevant (≥10 points) for all KOOS-subscales, except Sport/Rec whereas, no between-groups difference in the primary outcome KOOS ADL (3.6 [-2.1 to 9.2]; P = 0.216) was observed. For KOOS Symptoms, a statistically significant difference of 7.6 points (2.6-12.7; P = 0.004) was observed in favor of NEMEX with 47% improving ≥10 points.

CONCLUSIONS: No difference in improvement in difficulty with ADL was observed. NEMEX improved knee symptoms to a greater extent with half of patients reporting clinically relevant improvements. CLINICALTRIALS.

There are increasing needs for detailed real-world data on rheumatic diseases and their treatments. Clinical register data are essential sources of information that can be enriched through linkage to additional data sources such as national health data registers. Detailed analyses call for international collaborative observational research to increase the number of patients and the statistical power. Such linkages and collaborations come with legal, logistic and methodological challenges. In collaboration between registers of inflammatory arthritides in Sweden, Denmark, Norway, Finland and Iceland, we plan to enrich, harmonise and standardise individual data repositories to investigate analytical approaches to multisource data, to assess the viability of different logistical approaches to data protection and sharing and to perform collaborative studies on treatment effectiveness, safety and health-economic outcomes. This narrative review summarises the needs and potentials and the challenges that remain to be overcome in order to enable large-scale international collaborative research based on clinical and other types of data.

BACKGROUND: Over the last 20 years, there have been marked improvements in the availability of effective medications for rheumatic conditions such as gout, osteoporosis and rheumatoid arthritis (RA), which have led to a reduction in disease flares and the risk of re-fracture in osteoporosis, and the slowing of disease progression in RA. However, medication adherence remains suboptimal, as treatment regimens can be complex and difficult to continue long term. Many trials have been conducted to improve adherence to medication. Core domains, which are the outcomes of most relevance to patients and clinicians, are a pivotal component of any trial. These core domains should be measured consistently, so that all relevant trials can be combined in systematic reviews and meta-analyses to reach conclusions that are more valid. Failure to do this severely limits the potential for trial-based evidence to inform decisions on how to support medication adherence. The Outcome Measures in Rheumatology (OMERACT) - Interventions for Medication Adherence study by the OMERACT-Adherence Group aims to develop a core domain set for interventions that aim to support medication adherence in rheumatology.

METHODS/DESIGN: This OMERACT-Adherence study has five phases: (1) a systematic review to identify outcome domains that have been reported in interventions focused on supporting medication adherence in rheumatology; (2) semi-structured stakeholder interviews with patients and caregivers to determine their views on the core domains; (3) focus groups using the nominal group technique with patients and caregivers to identify and rank domains that are relevant to them, including the reasons for their choices; (4) an international three-round modified Delphi survey involving patients with diverse rheumatic conditions, caregivers, health professionals, researchers and other stakeholders to develop a preliminary core domain set; and (5) a stakeholder workshop with OMERACT members to review, vote on and reach a consensus on the core domain set for interventions to support medication adherence in rheumatology.

DISCUSSION: Establishing a core domain set to be reported in all intervention studies undertaken to support patients with medication adherence will enhance the relevance and the impact of these results and improve the lives of people with rheumatic conditions.

Background: Biomechanical studies show varying results regarding the elongation of adjustable fixation devices. This has led to growing concern over the stability of the ToggleLoc with ZipLoop used in anterior cruciate ligament (ACL) reconstruction (ACLR) in vivo.

Purpose/Hypothesis: The purpose of this study was to compare passive knee stability 1 year after ACLR in patients in whom the Endobutton or ToggleLoc with ZipLoop was used for femoral graft fixation. The hypothesis was that the ToggleLoc with ZipLoop would be inferior in knee stability to the Endobutton 1 year after primary ACLR.

Study Design: Cohort study; Level of evidence, 2.

Methods: Data from 3175 patients (Endobutton: n = 2807; ToggleLoc with ZipLoop: n = 368) were included from the Danish Knee Ligament Reconstruction Registry (DKRR) between June 2010 and September 2013. Data were retrieved from standardized ACL forms filled out by the operating surgeon preoperatively, during surgery, and at a clinical examination 1 year after surgery. Passive knee stability was evaluated using 1 of 2 arthrometers (Rolimeter or KT-1000 arthrometer) and the pivot-shift test. Using the same database, the number of reoperations performed up to 4 years after primary surgery was examined.

Results: Full data were available for 1654 patients (Endobutton: n = 1538; ToggleLoc with ZipLoop: n = 116). ACLR with both devices resulted in increased passive knee stability (P < .001). Patients who received the ToggleLoc with ZipLoop were found to have a better preoperative (P = .005 ) and postoperative (P < .001) pivot-shift test result. No statistically significant difference regarding the number of reoperations (P = .086) or the time to reoperation (P = .295) was found.

Conclusion: Patients who underwent fixation with the ToggleLoc with ZipLoop had improved passive knee stability 1 year after surgery, measured by anterior tibial translation and pivot-shift test results, similar to patients who underwent fixation with the Endobutton. No difference was seen in knee stability or reoperation rates between the 2 devices.

OBJECTIVE: To study the impact of common noncomposite disease activity measures on sick leave in biologics-treated patients with rheumatoid arthritis (RA).

METHODS: Data from study visits by biologics-treated RA patients of working age (<65 years) in the observational South Swedish Arthritis Treatment Group Register between 2005 and 2011, were included (5,118 visits by 941 patients). We performed association analyses between various noncomposite disease activity measures at each visit and the number of days of sick leave during the subsequent month; this information was retrieved from the Social Insurance Agency. Adjusted separate generalized estimating equation regression models were used, and analyses were stratified according to sick leave status for the month preceding each visit (no, partial, or full sick leave). Results are presented as standardized beta coefficients for comparability.

RESULTS: Among modifiable noncomposite disease activity measures, patient's assessment of pain and disease activity scored on a visual analog scale (VAS) were most strongly associated with subsequent sick leave, irrespective of baseline sick leave status. Generally, measures that were more objective (swollen joint count, erythrocyte sedimentation rate, and C-reactive protein) had less impact on sick leave compared with variables that were more subjective (patient's pain and global scores on a VAS, evaluator's global assessment of disease activity on a 5-grade Likert scale, and tender joint count).

CONCLUSION: Measures of disease activity that are more subjective have a greater impact on sick leave in biologics-treated patients with RA compared with variables that are more objective, suggesting a stronger focus on subjective measures when targeting work loss or intervening to reduce it.

BACKGROUND: To evaluate the trends in treatment of patellar dislocation in the Danish population as a whole from 1996 to 2014 and evaluate the incidence of persistent morbidity after Medial Patellofemoral Ligament Reconstruction (MPFL-R).

METHODS: This epidemiological study was performed by retrospectively searching the Danish National Patients Registry from 1996 to 2014. The study investigated the trends in surgery performed on patients with patellar dislocations and the risk of persistent patellar morbidity (PPM) with an eight-year follow-up. PPM was defined as a new patella-related contact to the healthcare system more than a year after surgery.

RESULTS: From 1996 to 2014, a total of 1956 MPFL-R were performed in Denmark. In 2014, MPFL-R constituted 75% of all patella-stabilizing surgery and was performed on almost 10% of patients with patellar dislocation. The mean risk of PPM eight years after surgery was 20.9% (18.3-23.4%), and young patients aged 10-17 showed the highest risk of 28.9% (23.7-33.7%). The risk of PPM over time was significantly higher for other patella-stabilizing surgery (33.8%) and patients receiving conservative treatment (29.4%) compared to MPFL-R.

CONCLUSIONS: A rapid rise in the use of MPFL-R was found from 2005 to 2014, constituting 75% of all patella-stabilizing surgery in 2014. The overall risk of persistent patellar morbidity within eight years after MPFL-R was 21%. MPFL-R was found to give a significantly lower risk of PPM over time as compared to other patella-stabilizing surgery and conservative treatment.

METHODS: We included 180 disease-modifying antirheumatic drug-naive patients with early rheumatoid arthritis (RA) randomized to adalimumab (ADA; n = 89) or placebo (n = 91) in combination with MTX. Plasma samples before and 3 months after treatment initiation were analyzed for 91 specific miRNA by quantitative reverse transcriptase-polymerase chain reaction on microfluidic dynamic arrays. A linear mixed-effects model was used to test for associations between pretreatment miRNA and changes in miRNA expression and American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) Boolean (28 joints) remission at 3 and 12 months, applying false discovery rate correction for multiple testing. Using leave-one-out cross validation, we built predictive multivariate miRNA models and estimated classification performances using receiver-operating characteristics (ROC) curves.

RESULTS: In the ADA group, a higher pretreatment level of miR-27a-3p was significantly associated with remission at 12 months. The level decreased in remitting patients between pretreatment and 3 months, and increased in nonremitting patients. No associations were found in the placebo group receiving only MTX. Two multivariate miRNA models were able to predict response to ADA treatment after 3 and 12 months, with 63% and 82% area under the ROC curves, respectively.

CONCLUSION: We identified miR-27a-3p as a potential predictive biomarker of ACR/EULAR remission in patients with early RA treated with ADA in combination with MTX. We conclude that pretreatment plasma-miRNA profiles may be of predictive value, but the results need confirmation in independent cohorts.

Background It has been demonstrated that weight loss improves symptoms in obese subjects with knee osteoarthritis (KOA). A parallel change in cartilage morphology remains to be demonstrated. Purpose To demonstrate a parallel change in cartilage morphology. Material and Methods Obese patients with KOA were examined before and after weight loss over 16 weeks. Target knee joints were radiographically assessed by the Kellgren/Lawrence grading (KLG) system. Patients with KLG-1 and 2 changes in the lateral compartment were included. Delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) was performed using intra-articular contrast. Results Nine patients with lateral KLG-1 and ten patients with lateral KLG-2 were studied. There were no group differences regarding the lateral compartment baseline dGEMRIC T1 values: median = 497 ms (KLG-1) and 533 ms (KLG-2) ( P = 0.12), or regarding reduction in body mass index (BMI) after 16 weeks: 12.8% versus 11.4% ( P = 0.74). In the KLG-1 group, several cases of increased dGEMRIC T1 values were seen and median value decreased significantly less than in KLG-2 group (15 ms versus 41 ms, P = 0.03) after weight loss. Conclusion Improvement of cartilage quality, assessed with dGEMRIC, after weight loss might be possible in early stage KOA (KLG-1), but not in later stage KOA (KLG-2). The results may suggest a point of no return for improvement of cartilage quality that should be tested in larger trials.

OBJECTIVES: To investigate predictors of 10-year risk of revision and 1-year risk of prosthetic joint infection (PJI) and death following total hip/total knee arthroplasty (THA/TKA) in (1) patients with rheumatoid arthritis (RA) compared with patients with osteoarthritis (OA); and (2) patients with RA treated with biological disease-modifying antirheumatic drugs (bDMARD) within 90 days preceding surgery compared with non-treated.

METHODS: Register-based cohort study using the Danish National Patient Register, the DANBIO rheumatology register (RA-specific confounders and treatment episodes) and the Danish Hip and Knee Arthroplasty Registers. Survival analyses were used to calculate confounder-adjusted sub-HRs (SHR) and HRs.

RESULTS: In total, 3913 patients with RA with THA/TKA were compared with 120 499 patients with OA. Patients with RA had decreased risk of revision (SHR 0.71 (0.57-0.89)), but increased risk of PJI (SHR=1.46 (1.13-1.88)) and death (HR=1.25 (1.01-1.55)). In DANBIO, 345 of 1946 patients with RA with THA/TKA had received bDMARD treatment within 90 days preceding surgery. bDMARD-treated patients did not have a statistically significant increased risk of revision (SHR=1.49 (0.65-3.40)), PJI (SHR=1.61 (0.70-3.69)) nor death (HR=0.75 (0.24-2.33)) compared with non-treated. Glucocorticoid exposure (HR=2.87 (1.12-7.34)) and increasing DAS28 (HR=1.49 (1.01-2.20)) were risk factors for mortality.

CONCLUSION: Patients with RA had a decreased 10-year risk of revision while the risk of death and PJI was increased compared with patients with OA following THA/TKA. bDMARD exposure was not associated with statistically significant increased risk of neither PJI nor death in this study. Glucocorticoid exposure and increased disease activity were associated with an increased risk of death.

OBJECTIVES: The objective of this study was to estimate the prevalence of undiagnosed diabetes mellitus in patients with newly diagnosed frozen shoulder (FS) and study whether diabetes mellitus increases the severity of FS disease.

METHODS: Patients with newly diagnosed FS were consecutively included in this case-control study. Patients who were not already diagnosed as having diabetes mellitus were invited to be tested with the hemoglobin A1c blood sample test. The study population was compared with a control group, consisting of five individuals from the general population matched on age and sex. The passive range of motion, Oxford Shoulder Score, and visual analog scale (VAS) for average and maximum daily pain was recorded for all of the patients in the study group.

RESULTS: A total of 235 patients were included, 34 (14%) of whom were diagnosed as having diabetes mellitus before the examination. Of the remaining 201 patients, 122 (61%) agreed to be tested for diabetes mellitus. None of the tested patients had undiagnosed diabetes mellitus. This was not significantly different from the prevalence in the matched control population (P = 0.09). There was no difference between patients with and without diabetes mellitus in average daily VAS (P = 0.46) nor maximum daily VAS (P = 0.44). The Oxford Shoulder Score was similar in the two groups (P = 0.23) as was the range of motion.

CONCLUSIONS: The prevalence of undiagnosed diabetes mellitus is low in patients with FS and does not differ from the general population. Diabetes mellitus does not seem to affect patients' perceived severity of an FS.

BACKGROUND: Rotator cuff tear is a common cause of shoulder disability and results in patients predominantly complaining of pain and loss of motion and strength. Traumatic rotator cuff tears are typically managed surgically followed by ~ 20 weeks of rehabilitation. However, the timing and intensity of the postoperative rehabilitation strategy required to reach an optimal clinical outcome is unknown. Early controlled and gradually increased tendon loading has been suggested to positively influence tendon healing and recovery. The aim of this trial is therefore to examine the effect of a progressive rehabilitation strategy on pain, physical function and quality of life compared to usual care (that limits tendon loading in the early postoperative phase) in patients who have a rotator cuff repair of a traumatic tear.

METHODS: The current study is a randomized, controlled, outcome-assessor blinded, multicenter, superiority trial with a two-group paralleled design. A total of 100 patients with surgically repaired traumatic rotator cuff tears will be recruited from up to three orthopedic departments in Denmark, and randomized to either a progressive early passive and active movement program or a limited early passive movement program (usual care). The primary outcome measure will be the change from pre-surgery to 12 weeks post-surgery in the Western Ontario Rotator Cuff Index questionnaire. Secondary outcomes include the Disabilities Arm, Shoulder and Hand questionnaire (DASH), range of motion, strength and tendon healing characteristics from ultrasound measurements at 12 months follow up.

DISCUSSION: We hypothesized that patients who receive the progressive rehabilitation strategy will benefit more with respect to pain reduction, physical function and quality of life than those who receive care as usual. If this is confirmed our study can be used clinically to enhance the recovery of patients with traumatic rotator cuff tear.

INTRODUCTION: The provision of healthcare for patients with inflammatory arthritis occurs in the context of somewhat conflicting targets, values and drivers. Therefore, there is a need for introducing 'value-based healthcare' defined as the value of patient relevant health outcomes in relation to costs. This term is a central part of tomorrow's healthcare sector, especially for rheumatic diseases, yet the transition is a huge challenge, as it will impact the development, delivery and assessment of healthcare.

AIMS: The aim of this study is to compare medical and patient evaluated impact of the traditional settlement and financing production (DAGS) controlled healthcare setting with a value-based and patient-centred adjunctive to standard care.

METHODS AND ANALYSIS: Patients with inflammatory arthritis receiving treatment in routine care at the outpatient clinics in the Capital Region of Denmark will prospectively and consecutively be enrolled in a Non-Intervention-Study framework providing a pragmatic value-based management model. A Danish reference cohort, used for comparison will be collected as part of routine clinical care. The enrolment period will be from 1 June 2018 until 31December 2023. Baseline and follow-up visits will be according to routine clinical care. Registry data will be obtained directly from patients and include personal, clinical and outcomes information. The study results will be reported in accordance with the STROBE statement.

ETHICS AND DISSEMINATION: The study has been notified to the Danish Data Protection Agency and granted authorisation for the period June 2018 to January 2025 (pending). Informed consent will be obtained from all patients before enrolment in the study. The study is approved by the ethics committee, Capital Region of Denmark (H-18013158). Results of the study will be disseminated through publication in international peer-reviewed journals.

OBJECTIVE: To assess the effect of quadriceps strengthening on quadriceps muscle force, power, and work and tibio-femoral compressive loads during walking in adults with knee osteoarthritis.

METHODS: Study design: Two-center, randomized, controlled trial.

INTERVENTION: Patients with knee osteoarthritis were randomly allocated to quadriceps strengthening program (3 times weekly) or no attention control group.

MAIN OUTCOME MEASURES: Primary outcome was change from baseline in peak quadriceps force during walking at 12 weeks. Secondary outcomes included quadriceps power and work, knee compression forces during walking estimated with musculoskeletal modeling, muscle strength and pain and function. Outcomes were measured at baseline and 12 weeks.

RESULTS: 30 patients were randomized to receive either training (n = 15) or no attention (n = 15). At follow-up, there were no statistical differences between groups for maximum quadriceps force, quadriceps positive power, negative work, and positive work, and knee compressive force. Maximum negative quadriceps power in early stance was statistically significantly increased 36% in the training group compared to the control group which was most likely partially a response to faster walking velocity at follow-up. Muscle strength and patient reported pain and function were improved in the training group compared to the control group.

Clinical practice guidelines can assist rheumatologists in the proper prescription of newer treatment for rheumatoid arthritis (RA). The objective of this paper is to report on the recommendations for the management of patients with RA in the Eastern Mediterranean region. We adapted the 2015 American College of Rheumatology guidelines in two separate waves. We used the adolopment methodology, and followed the 18 steps of the "Guidelines 2.0" comprehensive checklist for guideline development. For each question, we updated the original guidelines' evidence synthesis, and we developed an Evidence Profile (EP) and an Evidence to Decision (EtD) table. In the first wave, we adoloped eight out of the 15 original questions on early RA. The strength changed for five of these recommendations from strong to conditional, due to one or more of the following factors: cost, impact on health equities, the balance of benefits, and harms and acceptability. In the second wave, we adoloped eight out of the original 44 questions on established RA. The strength changed for two of these recommendations from strong to conditional, in both cases due to cost, impact on health equities, balance of benefits and harms, and acceptability. The panel also developed a good practice recommendation. We successfully adoloped 16 recommendations for the management of early and established RA in the Eastern Mediterranean region. The process proved feasible and sensitive to contextual factors.

BACKGROUND: Cigarette smoking is associated with earlier menopause, but the impact of being a former smoker and any dose-response relationships on the degree of smoking and age at menopause have been less clear. If the toxic impact of cigarette smoking on ovarian function is irreversible, we hypothesized that even former smokers might experience earlier menopause, and variations in intensity, duration, cumulative dose, and age at start/quit of smoking might have varying impacts on the risk of experiencing earlier menopause.

METHODS AND FINDINGS: A total of 207,231 and 27,580 postmenopausal women were included in the cross-sectional and prospective analyses, respectively. They were from 17 studies in 7 countries (Australia, Denmark, France, Japan, Sweden, United Kingdom, United States) that contributed data to the International collaboration for a Life course Approach to reproductive health and Chronic disease Events (InterLACE). Information on smoking status, cigarettes smoked per day (intensity), smoking duration, pack-years (cumulative dose), age started, and years since quitting smoking was collected at baseline. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRRs) and 95% confidence intervals (CIs) for the associations between each smoking measure and categorised age at menopause (<40 (premature), 40-44 (early), 45-49, 50-51 (reference), and ≥52 years). The association with current and former smokers was analysed separately. Sensitivity analyses and two-step meta-analyses were also conducted to test the results. The Bayesian information criterion (BIC) was used to compare the fit of the models of smoking measures. Overall, 1.9% and 7.3% of women experienced premature and early menopause, respectively. Compared with never smokers, current smokers had around twice the risk of experiencing premature (RRR 2.05; 95% CI 1.73-2.44) (p < 0.001) and early menopause (1.80; 1.66-1.95) (p < 0.001). The corresponding RRRs in former smokers were attenuated to 1.13 (1.04-1.23; p = 0.006) and 1.15 (1.05-1.27; p = 0.005). In both current and former smokers, dose-response relationships were observed, i.e., higher intensity, longer duration, higher cumulative dose, earlier age at start smoking, and shorter time since quitting smoking were significantly associated with higher risk of premature and early menopause, as well as earlier menopause at 45-49 years. Duration of smoking was a strong predictor of age at natural menopause. Among current smokers with duration of 15-20 years, the risk was markedly higher for premature (15.58; 11.29-19.86; p < 0.001) and early (6.55; 5.04-8.52; p < 0.001) menopause. Also, current smokers with 11-15 pack-years had over 4-fold (4.35; 2.78-5.92; p < 0.001) and 3-fold (3.01; 2.15-4.21; p < 0.001) risk of premature and early menopause, respectively. Smokers who had quit smoking for more than 10 years had similar risk as never smokers (1.04; 0.98-1.10; p = 0.176). A limitation of the study is the measurement errors that may have arisen due to recall bias.

CONCLUSIONS: The probability of earlier menopause is positively associated with intensity, duration, cumulative dose, and earlier initiation of smoking. Smoking duration is a much stronger predictor of premature and early menopause than others. Our findings highlight the clear benefits for women of early smoking cessation to lower their excess risk of earlier menopause.

Physical inactivity is important to address, and an objective way of measuring inactivity is by accelerometry. The objective of this study was to determine the reliability and construct validity of the SENS motion system to record physical activity and inactivity in patients with knee osteoarthritis. Participants with an age > 40 years and an average weekly pain above 0 on a numeric rating scale (0 = no pain, 10 = worst pain) were included. Participants had a total of two study visits and at each visit participants completed a standardized activity. Data from 24 participants were analysed. A mean agreement of 99% (SD 3%) for sedentary behaviour and a mean agreement of 97% (SD 9%) for active behaviour were found. The agreement for "walking" was 28% (SD 18%). Mean agreement between recordings on the two visits was 96% (SD 8%) for sedentary behaviour and 99% (SD 1%) for active behaviour. The SENS motion activity measurement system can be regarded as a reliable and valid device for measuring sedentary behaviour in patients with knee OA, whereas detection of walking is not reliable and would require further work.